Decapentaplegic in the aging fly gonad

A major emerging theme in stem cell biology is that the tissue microenvironment or “niche” — the cells that surround, support, and communicate with stem cells — are critical for their proper function, and in particular for their persistence and health over the course of aging. Stem cells seem to fare poorly in aged niches — an observation with major ramifications regarding the prospects of treating late-life diseases (or aging per se) by simply re-introducing stem cells to decrepit organs.

The fruit fly gonad is an important model system for stem cell and niche aging: in both males and females, the organ undergoes dramatic changes over the course of the lifespan, and in both sexes, decreases in the numbers and capacity of functional germline stem cells (GSCs) occurs at least in part due to deterioration of the niche. (For an excellent and fairly current review of the subject, see here.)

Late last year, we learned that declining BMP and E-cadherin signaling from ovarian niche cells appears to be responsible for the decline in GSCs in the female gonad. (In the testis, E-cadherin is also important, along with another signaling molecule, unpaired.) Now a new player has been revealed: Zhao et al. report that decapentaplegic signaling from the ovarian niche also declines with age, and that this may have a causative role in the diminution of GSC number and proliferative capacity:

Adult stem cells are important in replenishing aged cells to maintain tissue homeostasis. Aging in turn may exert profound effects on stem cell’s regenerative potential, but to date the mechanisms of such stem cell aging are poorly understood, and it is not clear to what extent stem cell aging contributes to tissue or organ aging. Here we show in female Drosophila, that germline stem cell (GSC) division rate progressively declines with age, which is accompanied by reduced decapentaplegic (dpp) niche signaling pathway activation within GSCs. Egg production also rapidly declines with age, which is accompanied by both decreased stem cell division and increased incidence of cell death of developing eggs, especially in the oldest females. Genetically increasing dpp expression delays GSC activity decline and transiently increases egg production. We conclude that age-related decline of reproduction is caused by both decreased GSC activity and increased incidence of cell death during oogenesis, while decreased GSC activity is attributed to declined signaling from the regulatory niche. We suggest that niche functional decay may be an important mechanism for stem cell aging and system failure.

Taken together with last year’s results, this paper informs us that — perhaps not surprisingly — there are multiple signals between the niche and the GSCs. I find it somewhat curious that both BMP and decapentaplegic overexpression can delay GSC aging; this observation suggests that the two factors may be rate-limiting at different stages of the aging process — or alternately, that they ultimately converge on the same intracellular signal relevant to GSC viability.